Conservation of Total T-Cell Counts During HIV Infection: Alternative Hypotheses and Implications

Grossman, Zvi; Herberman, Ronald B.; Vatnik, Nurit; Intrator, Nathan

doi:10.1097/00042560-199804150-00010

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…There was also a positive correlation between the percentage (although of low statistical significance) and absolute counts (P < 0·0001) of CD8 þ CD28 þ cells and CD4 þ T cells. These results suggest the existence of a homeostatic regulation inside the T cell compartment [17], operating at least in peripheral blood [37], by which losses of CD4 þ and CD8 þ CD28 þ cells are balanced by an increased number of CD8 þ CD28 ¹ cells, as recently proposed by Caruso et al [38]. This interpretation is supported by our observation that the coefficient of variation (CV) of the percentage of total T cells (CV 8·3%) was much smaller than either the CV of the percentage of CD4 þ plus CD8 þ CD28 þ cells (CV 33·2%) or that of the percentage of CD8 þ CD28 ¹ cells (CV 31·5%).…”

Section: Discussionmentioning

confidence: 72%

Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment

Bürgisser¹,

HAMMANN²,

Kaufmann

et al. 1999

Clinical and Experimental Immunology

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The relationship between blood CD8+ T lymphocyte subsets, as defined by CD28 and CD38 expression, and plasma viraemia and CD4+ T cells in HIV-1 infection was investigated. In a cross-sectional study of 46 patients with either no or stable anti-retroviral treatment, there was a strong negative correlation between the percentage of CD8+CD28- and the percentage of CD4+ T cells (r = -0.75, P < 0.0001), and a positive correlation between absolute numbers of CD8+CD28+ and CD4+ T cells (r = 0.56, P < 0.0001). In contrast, the expression of CD38 by CD8+ T lymphocytes correlated primarily with plasma viraemia (e.g. the percentage of CD38+ in CD8bright cells, r = 0.76, P < 0.0001). In the 6 months following triple therapy initiation in 32 subjects, there was a close correlation between changes (delta) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. delta % CD8+CD28+ versus delta % CD4+, r = 0.37, P = 0.0002; delta % CD8+CD28- versus delta % CD4+, r = -0.66, P < 0.0001). A marked decline of the number of CD8+ T cells expressing CD38 was also observed. These results suggest the existence of a T cell homeostasis mechanism operating in blood with CD4+ and CD8+CD28+ cells on the one hand, and with CD8+CD28- cells on the other. In addition, the percentage of CD38+ cells in CD8+ cells, generally considered an independent prognostic factor, could merely reflect plasma viral load.

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Section: Discussionmentioning

confidence: 72%

Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment

Bürgisser¹,

HAMMANN²,

Kaufmann

et al. 1999

Clinical and Experimental Immunology

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“…CD4+ and CD8+ T-cell counts tend to change progressively and in opposite directions in HIV infection [26]. T-cell subpopulation homeostasis is maintained by complex regulatory mechanisms that are still not fully understood [27].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms controlling CD8+ T-cell homeostasis may obscure, delay or impede CD8+ T-cell responses following cART initiation and hence, prevent normalization of the CD4:CD8 ratio despite independent increases in the CD4+ T-cells. It has been proposed that homeostasis of total T-cells in the peripheral blood occurs by replacement with either CD4+ or CD8+ T-cells as CD4+ T-cells are depleted [31].This “blind T-cell homeostasis” theory has been challenged [26] where the mechanisms controlling this homeostasis in HIV infection may fail. In the end, the factors controlling homeostasis of T-cells, and the best marker of altered homeostasis, have yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy

et al. 2013

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BackgroundHIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death.MethodsA Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000–2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models.Results4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm3, baseline CD8+ T-cells <500 cells/mm3, time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death.ConclusionsIn our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.

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“…Overall, in our experimental system the homeostasis of CD8 ϩ T cells appeared to be, by and large, lineage specific and thus regulated separately from that of CD4 ϩ T cells. The finding of a lineage-specific proliferation of CD8 ϩ T cells after Ab-mediated CD8 ϩ T cell depletion argues against the presence of a "blind" (i.e., incapable of distinguishing between CD4 ϩ and CD8 ϩ T cells) homeostasis of T cells in primates and mice (57)(58)(59). However, the fact that the homeostasis of CD4 ϩ and CD8 ϩ T cells is regulated separately in primates will need to be confirmed in future studies in which CD4 ϩ T cells are depleted with anti-CD4 Abs and the reconstitution of the CD4 ϩ T cell pool is followed over time.…”

Section: Discussionmentioning

confidence: 99%

Depletion of CD8+ Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species

Barry

Silvestri

Safrit

et al. 2007

The Journal of Immunology

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SIV infection of sooty mangabeys (SMs), a natural host species, does not cause AIDS despite high-level virus replication. In contrast, SIV infection of nonnatural hosts such as rhesus macaques (RMs) induces an AIDS-like disease. The depletion of CD8+ T cells during SIV infection of RMs results in marked increases in plasma viremia, suggesting a key role for CD8+ T cells in controlling levels of SIV replication. To assess the role that CD8+ T cells play in determining the virologic and immunologic features of nonpathogenic SIV infection in SMs, we transiently depleted CD8+ T cells in SIV-infected and uninfected SMs using a CD8α-specific Ab (OKT8F) previously used in studies of SIV-infected RMs. Treatment of SMs with the OKT8F Ab resulted in the prompt and profound depletion of CD8+ T cells. However, in contrast to CD8+ cell depleted, SIV-infected RMs, only minor changes in the levels of plasma viremia were observed in most SIV-infected SMs during the period of CD8+ cell deficiency. Those SMs demonstrating greater increases in SIV replication following CD8+ cell depletion also displayed higher levels of CD4+ T cell activation and/or evidence of CMV reactivation, suggesting that an expanded target cell pool rather than the absence of CD8+ T cell control may have been primarily responsible for transient increases in viremia. These data indicate that CD8+ T cells exert a limited influence in determining the levels of SIV replication in SMs and provide additional evidence demonstrating that the absence of AIDS in SIV-infected SMs is not due to the effective control of viral replication by cellular immune responses.

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Conservation of Total T-Cell Counts During HIV Infection: Alternative Hypotheses and Implications

Cited by 8 publications

References 8 publications

Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment

Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment

Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy

Depletion of CD8+ Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species

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